This invention relates to novel compounds which are useful as topical antimicrobial agents and more particularly to antimicrobial compounds which are effective against the microorganisms that produce dental plaque, which have a prolonged intraoral residence time and antimicrobial activity, which have an acceptable taste, and which do not stain the teeth or gums.
Dental plaque is a soft, tenacious bacterial deposit which forms on the surface of the teeth. It is produced by the action of certain bacteria viz., S. mutans, A. viscosus, and A. naeslundi, on carbohydrate substances in the mouth. Of the numerous antimicrobial agents that have been investigated for their ability to inhibit plaque formation, only 1,6-bis-(p-chlorophenylbiguanidino)hexane (chlorhexidine) and 1,6-bis-(2-ethylhexylbiguanidino)hexane (alexidine) are reported to be clinically effective antiplaque agents. However, because these agents are extremely strong organic bases, and consequently are almost entirely cationic at the prevailing pH of the mouth, they suffer from the following disadvantages: (1) they are extremely bitter-tasting substances with a prolonged bitter after-taste lasting up to several hours, (2) they alter taste perception of foodstuffs for several hours, (3) with prolonged use they produce stains of various colors on the teeth, tongue, gums, oral mucosa, (4) they produce local irritation of the oral mucosa and tongue.
A class of carbamylguanidine topical antimicrobial compounds which avoids some of the deficiencies of the prior art compounds is disclosed in U.S. patent application Ser. No. 546,549, now U.S. Pat. No. 4,022,962. This application discloses further carbamylguanidine antimicrobial compounds having improved properties with respect to both the bis-biguanide antimicrobials and the compounds of U.S. Ser. No. 546,549, now U.S. Pat. No. 4,022,962.